6faw - Revision history

OCA at 15:57, 27 February 2019

OCA — Wed, 27 Feb 2019 15:57:59 GMT

←Older revision		Revision as of 15:57, 27 February 2019
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	==See Also==		==See Also==
	*[[Tau protein\|Tau protein]]		*[[Tau protein\|Tau protein]]
		+	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:01, 2 December 2018

OCA — Sun, 02 Dec 2018 21:01:11 GMT

←Older revision		Revision as of 21:01, 2 December 2018
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	<StructureSection load='6faw' size='340' side='right' caption='[[6faw]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='6faw' size='340' side='right' caption='[[6faw]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6faw]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FAW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6faw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FAW FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D3K:(2~{R})-2-[(~{R})-[2-(2-methoxyethoxy)phenyl]-phenyl-methyl]pyrrolidine'>D3K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D3K:(2~{R})-2-[(~{R})-[2-(2-methoxyethoxy)phenyl]-phenyl-methyl]pyrrolidine'>D3K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6fau\|6fau]], [[6fav\|6fav]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6fau\|6fau]], [[6fav\|6fav]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6faw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6faw OCA], [http://pdbe.org/6faw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6faw RCSB], [http://www.ebi.ac.uk/pdbsum/6faw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6faw ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6faw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6faw OCA], [http://pdbe.org/6faw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6faw RCSB], [http://www.ebi.ac.uk/pdbsum/6faw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6faw ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 6faw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6faw" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tau protein\|Tau protein]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Andrei, S A]]		[[Category: Andrei, S A]]
	[[Category: Meijer, F A]]		[[Category: Meijer, F A]]

OCA at 05:35, 16 May 2018

OCA — Wed, 16 May 2018 05:35:42 GMT

←Older revision		Revision as of 05:35, 16 May 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6faw is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of C-terminal modified Tau peptide-hybrid 4.2c-I with 14-3-3sigma==
		+	<StructureSection load='6faw' size='340' side='right' caption='[[6faw]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6faw]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FAW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D3K:(2~{R})-2-[(~{R})-[2-(2-methoxyethoxy)phenyl]-phenyl-methyl]pyrrolidine'>D3K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6fau\|6fau]], [[6fav\|6fav]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6faw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6faw OCA], [http://pdbe.org/6faw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6faw RCSB], [http://www.ebi.ac.uk/pdbsum/6faw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6faw ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Current molecular hypotheses have yet to deliver marketable treatments for Alzheimer's disease (AD), arguably due to a lack of basic knowledge of AD biology, and an overreliance on conventional drug modalities. Protein-protein interactions (PPIs) are emerging drug targets, which show promise for the treatment of e.g. cancer, but are still underexploited for treating neurodegenerative diseases. 14-3-3 binding to phosphorylated Tau is a promising PPI drug target based on its reported destabilizing effect on microtubules, leading to enhanced neurofibrillary tangle formation as a potential cause of AD-related neurodegeneration. Inhibition of 14-3-3/Tau may therefore be neuroprotective. Previously, we reported the development of modified peptide inhibitors of 14-3-3/Tau using a novel structure-guided approach. Here, we report further efforts to optimize the binding mode and activity of our modified Tau peptides through a combination of chemical synthesis, biochemical assays, X-ray crystallography and NMR spectroscopy studies. Most notably, we were able to characterize two different high-affinity binding modes, both of which inhibited 14-3-3-binding to full-length PKA-phosphorylated Tau protein in vitro. Our findings, besides producing useful tool inhibitor compounds for studying 14-3-3/Tau, have enhanced our understanding of the molecular parameters for inhibiting 14-3-3/Tau, which are important milestones toward the establishment of our 14-3-3 PPI hypothesis.

-	~~Authors: Andrei, S.A~~., ~~Meijer~~, F~~.A.~~, ~~Ottmann~~, C., Milroy~~, L~~.G.	+	Inhibition of 14-3-3/Tau by hybrid small-molecule-peptides operating via two different binding modes.,Andrei SA, Meijer F, Neves J, Brunsveld L, Landrieu I, Ottmann C, Milroy LG ACS Chem Neurosci. 2018 May 3. doi: 10.1021/acschemneuro.8b00118. PMID:29722962<ref>PMID:29722962</ref>

-	~~Description: Crystal structure~~ of ~~C-terminal modified Tau peptide-hybrid 4~~.2c-~~I with 14~~-~~3-3sigma~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Meijer, F.A]]	+	<div class="pdbe-citations 6faw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Andrei, S A]]
		+	[[Category: Meijer, F A]]
		+	[[Category: Milroy, L G]]
	[[Category: Ottmann, C]]		[[Category: Ottmann, C]]
-	[[Category: ~~Andrei, S.A~~]]	+	[[Category: Structural protein]]
-	[[Category: ~~Milroy, L.G~~]]	+	[[Category: Tau 14-3-3 alzheimer]]

OCA at 17:24, 24 January 2018

OCA — Wed, 24 Jan 2018 17:24:31 GMT

←Older revision		Revision as of 17:24, 24 January 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6faw is ON HOLD	+	The entry 6faw is ON HOLD until Paper Publication

	Authors: Andrei, S.A., Meijer, F.A., Ottmann, C., Milroy, L.G.		Authors: Andrei, S.A., Meijer, F.A., Ottmann, C., Milroy, L.G.

OCA: Protected "6faw" [edit=sysop:move=sysop]

OCA — Wed, 27 Dec 2017 07:30:41 GMT

Protected "6faw" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:30, 27 December 2017

OCA: New page: '''Unreleased structure''' The entry 6faw is ON HOLD Authors: Andrei, S.A., Meijer, F.A., Ottmann, C., Milroy, L.G. Description: Crystal structure of C-terminal modified Tau peptide-hy...

OCA — Wed, 27 Dec 2017 07:30:40 GMT

New page: '''Unreleased structure''' The entry 6faw is ON HOLD Authors: Andrei, S.A., Meijer, F.A., Ottmann, C., Milroy, L.G. Description: Crystal structure of C-terminal modified Tau peptide-hy...

New page

'''Unreleased structure'''

The entry 6faw is ON HOLD

Authors: Andrei, S.A., Meijer, F.A., Ottmann, C., Milroy, L.G.

Description: Crystal structure of C-terminal modified Tau peptide-hybrid 4.2c-I with 14-3-3sigma
[[Category: Unreleased Structures]]
[[Category: Meijer, F.A]]
[[Category: Ottmann, C]]
[[Category: Andrei, S.A]]
[[Category: Milroy, L.G]]